Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.

Objective To investigate the clinical efficacy and safety of 1 565 nm non-ablative fractional laser combined with topical minoxidil and oral finasteride in the treatment of patients with androgenetic alopecia(AGA).Methods Seventy-five male AGA patients with Norwood-Hamilton classification grade Ⅱ-Ⅲ,were randomly assigned into three groups:the control group 1,the control group 2 and the experimental group,with 25 cases in each group.Patients in the control group 1 received topical 5%minoxidil(1 mL,twice daily).Patients in the control group 2 were treated with both topical 5%minoxidil and oral finasteride(1 mg,once daily).Patients in the experimental group received a combined therapy of 1 565 nm non-ablative fractional laser in addition to topical 5%minoxidil and oral finasteride.Hair overall efficacy was evaluated using a 7-point rating scale after 24 weeks of treatment.Hair diameter and density were measured using a dermoscope.Patient satisfaction was assessed post-treatment,and adverse reactions were recorded.Results The overall efficacy of hair in the experimental group was superior to the control group 1 and the control group 2.There were no significant differences in hair density and hair diameter before treatment between the three groups(P＞0.05).After treatment,hair diameter and density increased in all three groups compared to baseline values(P＜0.05),and the hair diameter and hair density of the experimental group were higher than those of the control group 1 and the control group 2(P＜0.05).Patient satisfaction in the experimental group was higher than that in the control group 1 and the control group 2(P＜0.05).Patients in the experimental group experienced tolerable pain and burning sensations during laser treatment,and the symptoms were self-alleviated within a few hours.There were no serious adverse reactions reported in any group.Conclusion The combination therapy of 1 565 nm non-ablative fractional laser,5%minoxidil,and finasteride demonstrates significantly better efficacy in the treatment of AGA than minoxidil and finasteride alone drug therapy.

Objective:To compare the changes in pelvic floor electrophysiology and imaging in female patients with myofascial pelvic pain (MFPP), and to explore the characteristics and significance of these changes.Methods:A total of 49 MFPP patients who were admitted to the of Dalian Women′s and Children′s Medical Center (Group) from January 2019 to October 2021 were randomly selected as the research group, and 41 healthy women during the same period were selected as the control group. Both groups filled in the center′s medical history and general condition survey form. French PHENIX series pelvic floor muscle potential detection instrument was used to detect the resting vaginal muscle potential and maximum muscle potential of the two groups. The static tension, dynamic tension and pelvic floor muscle contraction force of the two groups were measured by French PHENIX series electronic tensioning apparatus with 5° and 10° opening respectively. Two dimensional transperineal ultrasound and three dimensional transvaginal ultrasound produced by B-K Company in Denmark were used to measure the length between the lower margin of the bladder neck from the symphysis pubis and the bladder neck and the bladder bottom (BND, BSD), the diameter of the genital tract hiatus and the angle of the anus and rectum. The area, anterior-posterior diameter, transverse diameter and different damage degrees of levator ani levator were measured.Results:The resting muscle potential of the study group was higher than that of the control group: 2 μV vs. 1 μV ( P<0.05); the maximum vaginal myopotential was higher than that of the control group: 7 μV vs. 6 μV ( P<0.05). The static tension, dynamic tension and contractile force: 204 g/m 2 vs. 175 g/m 2, 450 g/m 2 vs. 410 g/m 2 and 237 g/m 2 vs. 51 g/m 2 of pelvic floor muscle in the study group were higher than those in the control group when the tensioner was opened for 5° ( P<0.05). In resting state, BND, BSD and reproductive tract hiatus diameter in the study group were smaller than those in the control group: 14.0 mm vs. 16.7 mm, 15.3 mm vs. 19.7 mm, 46.7 mm vs. 49.5 mm ( P<0.05). The anal angle was greater than that of the control group: 129° vs. 112° ( P<0.05). The anal right angle in the study group was greater than that in the control group: 113° vs. 109° ( P<0.05). In the resting state, the area of levator ANI hiatus: 10.1 cm 2 vs. 11.6 cm 2, anterior and posterior diameters: 44.2 mm vs. 47.4 mm, transverse diameters and the defect scores of levator ani in the study group were all smaller than those in the control group ( P<0.05). Conclusions:MFPP presents with persistent pelvic floor muscle spasm and loss of coordination. MFPP can be treated by spasmolysis of pelvic floor muscle and fascia, which provides reference value for clinical treatment.

Immune escape mechanisms in non-small cell lung cancer (NSCLC) can disrupt every step of the anti-cancer immune response. In recent years, an increased understanding of the specific mechanisms fueling immune escape has allowed for the development of numerous immunotherapeutic treatments that have been introduced into the clinical practice. The advent of immunotherapy has dramatically changed the current treatment landscape of advanced or metastatic NSCLC because of its durable efficacy and manageable toxicity. In this review, we will first present a brief overview of recent evidence on immune escape mechanisms in NSCLC. We will then discuss the current promising immunotherapeutic strategies in advanced or metastatic NSCLC tumors.
Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms/drug therapy* ; Immunotherapy

Objective:To systematically review and evaluate the effect of small-dose naloxone on the development of nausea and vomiting during postoperative analgesia with opioid drugs in patients.Methods:Electronic Databases including Pubmed, Embase, Cochrane, Web of Science, China National Knowledge Infrastructure, Wanfang Data, China Biomedical Literature Database, and China Science and Technology Journal Database databases were searched from inception to May 2023 for randomized controlled trials involving the effect of small-dose naloxone on the development of adverse effects during postoperative analgesia with opioids. All randomized controlled trials enrolled included naloxone group and control group, the primary outcome was the incidence of postoperative nausea and vomiting, and the secondary outcome was postoperative VAS. Meta-analysis was performed using Stata 16.0 software.Results:Seven randomized controlled trials involving 542 patients were finally included in this meta-analysis. Compared with control group, the incidence of nausea and vomiting during postoperative analgesia was significantly decreased in naloxone group ( P<0.05), and no significant change was found in postoperative VAS scores ( P>0.05). Conclusions:Small-dose naloxone can reduce the development of nausea and vomiting during postoperative analgesia with opioid drugs.

Nonalcoholic steatohepatitis (NASH) is a spectrum of chronic liver disease characterized by hepatic lipid metabolism disorder. Recent reports emphasized the contribution of triglyceride and diglyceride accumulation to NASH, while the other lipids associated with the NASH pathogenesis remained unexplored. The specific purpose of our study was to explore a novel pathogenesis and treatment strategy of NASH via profiling the metabolic characteristics of lipids. Herein, multi-omics techniques based on LC-Q-TOF/MS, LC-MS/MS and MS imaging were developed and used to screen the action targets related to NASH progress and treatment. A methionine and choline deficient (MCD) diet-induced mouse model of NASH was then constructed, and Schisandra lignans extract (SLE) was applied to alleviate hepatic damage by regulating the lipid metabolism-related enzymes CES2A and CYP4A14. Hepatic lipidomics indicated that MCD-diet led to aberrant accumulation of phosphatidylethanolamines (PEs), and SLE could significantly reduce the accumulation of intrahepatic PEs. Notably, exogenous PE (18:0/18:1) was proved to significantly aggravate the mitochondrial damage and hepatocyte apoptosis. Supplementing PE (18:0/18:1) also deteriorated the NASH progress by up regulating intrahepatic proinflammatory and fibrotic factors, while PE synthase inhibitor exerted a prominent hepatoprotective role. The current work provides new insights into the relationship between PE metabolism and the pathogenesis of NASH.

Objective:To integrate the best evidence of non-drug intervention of urinary incontinence in elderly women and to formulate practical recommendations.Methods:In this systematic review study, using “elderly woman”,“urinary incontinence”,“bladder training”,“pelvic floor muscle training”,“enuresis”,“leakage of urine” as the key words, the 6S evidence resource pyramid model was used to search in British Medical Journal best practice, Uptodate, World Health Organization, Guidelines International Network, National Institute for Health and Care Excellence, Chinese Medical Association, Scottish Intercollegiate Guideline Network, Registered Nurses Association of Ontario, Cochrane Library, The Joanna Briggs Institute (JBI), New Zealand Guidelines Group, Polish Society of Gynecologists and Obstetricians, PubMed, Embase, Medline, Web of Science, SinoMed, China National Knowledge Infrastructure, WanFang Data, etc. The evidence retrieved included evidence-based knowledge base resources, clinical practice guidelines, expert consensus, systematic review, etc. Data were retrieved from January 1, 2017 to May 1, 2022, and collated from May 2, 2022 to May 25, 2022. Two researchers independently evaluated the quality of literature and extracted data using the AGREE Ⅱ and JBI evidence-based health care center assessment tools. The JBI evidence-based health care center′s evidence pre-rating system and evidence recommendation rating system were applied to rank the evidence; and under the guidance of the evidence structure of JBI, the strength of evidence recommendation was determined and the best evidence was extracted and summarized in combination with the study group discussion and expert opinion.Results:A total of 9 articles were retrieved, including 7 guidelines and 2 systematic reviews; and 6 guidelines were classified as Grade A and 1 as grade B; both 2 systematic reviews were rated as Grade A; 84% (27/32) of the items were evaluated as “Yes”. Evidence were summarized as 34 pieces of best evidence from 6 dimensions, including “overall recommendation, evaluation of type and degree of urinary incontinence, lifestyle change, behavioral therapy, prevention of precipitating factors, intervention in special population”; the flow chart of screening, evaluation, special symptoms, life style and behavior therapy was combed, and the practical suggestions were formed.Conclusions:The overall quality of the literature on non-drug intervention of urinary incontinence in elderly women is high, and the level of evidence is high. Early identification of urinary incontinence types and assessment of disease severity, lifestyle changes, avoidance of predisposing factors and behavioral therapy are the key to non-drug treatment of urinary incontinence in those patients.

AIM: To observe the effect ofacacia honey (AH) on serum uric acid level and renal function in potassium oxonate modelrats after drinking AH aqueous solution. METHODS: Sixty male SD rats were selected and randomly divided into control group (CON group), potassium oxonate model group (OA model group), 10% fructose group (10% F group) and different concentration honey groups (25%, 12.5% and 6.25% AH groups). All rats were fed with normal diet.The rats in CON group were subcutaneously injected with 5% sodium carboxymethyl cellulose (CMC-Na) solution and drunk sterile water every day, while rats in other groups were injected with 100 mg / kg OA solution suspended with 5% CMC-Na subcutaneouslyand drunksterile water orfructose solution or AH solution of different concentrations every day. Before and during the 4-week test, rats were weighed and blood was taken once a week. At the end of test, urine and feces specimens or kidney tissues were collected and blood was taken from the abdominal aorta. The uric acid content in blood, urine, and feces and the levels of serum creatinine (Cre) and blood urea nitrogen (BUN) or inflammatory factors in kidney tissues were measured. Renal function and histology were evaluated. RESULTS: Compared with CON group, AH could significantly reduce the body weight of rats (P<0.05), increase the kidney organ coefficient, the levels of serum uric acid, and uric acid in urine or feces, and reduce the level of fecal uric acid (FUA) in rats. AH can down regulate the level of tumor necrosis factor alpha (TNF-a) (P< 0.05) and up regulate the expression of monocyte chemoattractant protein 1 (MCP-1) and transforming growth factor β - 1 (TGF - β1) in rats kidneys; AH can cause slight to mild dilatation of renal tubules and mild to moderate basophilic lesions of renal rubules in rat kidney in a dose dependent manner. CONCLUSION: In the doses rang of present study, AH can cause hyperuricemia, renal tubular dilatation and basophilic lesions, and lead to renal function damage in rats.

Objective : To explore whether the NLRP3 inflammasome is activated after Newcastle disease virus (NDV) exposure to esophageal cancer ECA109 cells , whether its activation is related to K + efflux , and the effect of ATP/P2X7 axis on the activation of NLRP3 inflammasome. Methods: The expression of NLRP3 and IL⁃1β was detected by Western blot; the content of IL⁃1β in the supernatant was detected by ELISA ; the formation of ASC spots was detected by fluorescence immunoassay; the change of intracellular K + concentration was detected by fluorescent probe technology; Interventions with ATPase , ATP and P2X7 receptor inhibitors were used to investigate their role in NLRP3 inflammasome activation. Results: Compared with the control group , the expression of NLRP3 , IL⁃1β and ASC protein in cells was up⁃regulated after NDV F3 infection ; the intracellular potassium concen tration decreased with the prolongation of infection time (P < 0. 05) . After the intervention of P2X7 receptor inhibitor, the efflux of intracellular K + was blocked. With the increase of inhibitor concentration , the efflux of K + was maximally inhibited at 10 μmol/L (P < 0. 05) . The results of ATPase and ATP intervention showed that ATPase inhibited K + efflux , while ATP promoted K + efflux. Western blot results showed that compared with the control group , P2X7 receptor was inhibited , and the expressions of NLRP3 and IL⁃1β were down⁃regulated ; after ATPase intervened cells , the expressions of NLRP3 and IL⁃1β decreased ; After ATP intervention in cells , the protein expressions of NLRP3 and IL⁃1β were up⁃regulated (P < 0. 05) . Conclusion NDV F3 infection of ECA109 cells can activate the NLRP3 inflammasome , the mechanism may be related to the ATP/P2X7 axis.

Objective:To analyze the mediating effects of emotional changes in self-management interventions on the relationship between behavioral management and quality of life in elderly patients with type 2 diabetes and therefore to provide a reference for improving the emotional status of elderly diabetes patients and future community-based self-management interventions.Methods:From 2016 to 2020, a total of 69 self-management groups were formed in Hangzhou, each consisting of 10-15 patients with type 2 diabetes.Based on the construction of a medical consortium and family doctors signing up to provide services, intervention teams were established to conduct a series of group self-management activities for each group.Surveys via questionnaires were conducted before and after the intervention, as well as 6 months after the intervention, to collect patient data on demographics, disease status, emotions, quality of life, and self-management behaviors.The intervention effects were evaluated, and the correlations between emotional changes, self-management behaviors, and changes in quality of life were analyzed.Bootstrap analysis was used to test the mediating effects.Results:A total of 707 elderly diabetes patients were included.There were statistically significant differences in the scores of the Self-Rating Anxiety Scale(SAS), the Self-Rating Depression Scale(SDS), physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, mental health, physical component summary, mental component summary, the dietary control dimension of the type 2 diabetes self-care scale(2-DSCS), regular exercise, medication adherence, blood glucose monitoring, foot care, the dimension of prevention and management of hyperglycemia and hypoglycemia, and the total score of 2-DSCS( P<0.05 for all).Compared with pre-intervention, changes in SAS, SDS, physical component summary and mental component summary scores were all correlated with each dimension of 2-DSCS right after intervention and 6 months after intervention( r=-0.336-0.333, P<0.05), with the exception of changes in the blood glucose monitoring dimension score and changes in the emotional status score.The direct effect of self-management behavior on the quality of life in elderly patients with type 2 diabetes was 0.159, and the indirect effect through emotions was 0.229, with the mediating effect accounting for 59.02% of the total effect. Conclusions:Community-based group self-management activities can effectively improve the emotions and management behaviors of elderly diabetes patients and enhance their quality of life, Emotional changes play a certain mediating role between self-management behaviors and improvement in quality of life.